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40 Cards in this Set

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Where are the HLA/MHC genes found in humans?
Chromosme #6
Identify the three types of MHC molecules and where they are found.
Class I: most nucleated cells
Class II: professional APCs (m + B + dc)
Class III: secreted proteins found in serum
MHC I genes present to ____?

Gene locus is ____?
CD8+ Tcells (ex. Tc)

HLA-A, B & C in humans
MHC II genes present to ____?

Gene locus is ____?
CD4+ Tcells (Th)

HLA-DP, HLA-DQ, HLA-DR in humans
HLA definition
A gene product of the major histocompatibility complex; these antigens have been shown to have a strong influence on human allotransplantation, transfusions in refractory patients, and certain disease associations.
MHC III genes present to____?

Gene locus is ____?
do not directly present Ag to Tcells

code for:
complement Pr-
cytokines (TNF)
Ag processing Pr- (TAP, LMP2 & LMP7)
What is the difference between MHC I and MHC II?
I = single chain pr- associated with 2nd pr- not encoded for by MHC locus (beta2)
II: heterodimers coded for by the alpha and beta genes encoded within MHC locus
what is the beta 2 microglobulin?
the protein located within MHC I (an invariant chain) located on chromosome 15. it is the "crutch" which holds the Ag peptide area out to the Tcell
haplotype definition:
The alleles found on a single chromosome present at the known polymorphic sites in a gene or region of genomic DNA. The two haplotypes of a gene carried by an individual are that individual's alleles for the gene.
how many MHC I variants are there?

MHC II?
6 different MHC I

12 different MHC II
why are MHC proteins considered to be highly polymorphic?
1. co-dominant, both alleles expressed at once.
2. closely linked, low recombination frequency.
3. both alleles provide haplotype
why are MHC genes considered to be polygenic?
1. multiple similar genes
2. 6 class I and 12 class II
a. multiple dr-beta genes found in one person, and each can associate with the same/different dr-alpha genes. this increases diversity.
define classical MHC genes v. non-classical
c: T cell recognition of Ag
(HLA-a, b & c. HLA-dp, dr, dq)

n: NK cells and others
will the progeny of inbred mice be able to donate a graft to its parents?
receive a graft from its parents?
the progeny expresses BOTH haplotypes of the parents, so it can accept grafts from the parents. If the mother were to receive a graft from F1, it would be rejected as it contains the father's MHC.
with no recombination, what are the odds that siblings will be histocompatible?

with recombination?
25%


2%
what is the likelihood that two unrelated individuals have identical haplotypes?
almost zero
how does racial segregation affect this?
tissue transplants often need to be from members of the same racial background, due to specific recombinations within that population.
what is required within the MHC I molecule to bring it to the surface of the cell?
association of the large alpha chain with the invariant beta-2 microglobulin (which has no actual interaction with the Ag)
what are the three domains of the MHC I protein? what are their functions?
alpha 1 & 2 form the peptide binding cleft (8-10 aa)

alpha 3 interacts with CD8. it is structurally similar to beta-2 (via Ig constant region)and is relatively invariable.
what is the structure and function of the MHC II protein?
it's a heterodimer of alpha and beta chains, each is encoded for by different genes.

alpha 1/beta 1 = Ag binding cleft

alpha 2/beta 2 = CD4 contact area
MHC proteins are highly polymorphic because: (3)
1. co-dominant, both alleles expressed at once.
2. closely linked, low recombination frequency.
3. both alleles provide haplotype
MHC genes are polygenic because: (2)
1. multiple similar genes
2. 6 class I and 12 class II
a. multiple dr-beta genes found in one person, and each can associate with the same/different dr-alpha genes. this increases diversity.
define classical v. non-classical
c: T cell recognition of Ag
(HLA-a, b & c. HLA-dp, dr, dq)

n: NK cells and others
will the progeny of inbred mice be able to donate a graft to its parents?
receive a graft from its parents?
the progeny expresses BOTH haplotypes of the parents, so it can accept grafts from the parents. If the mother were to receive a graft from F1, it would be rejected as it contains the father's MHC.
with no recombination, what are the odds that siblings will be histocompatible?

with recombination?
25%


2%
what is the likelihood that two unrelated individuals have identical haplotypes?
almost zero
how does racial segregation affect this?
tissue transplants often need to be from members of the same racial background, due to specific recombinations within that population.
what is required within the MHC I molecule to bring it to the surface of the cell?
association of the large alpha chain with the invariant beta-2 microglobulin (which has no actual interaction with the Ag)
what are the three domains of the MHC I protein? what are their functions?
alpha 1 & 2 form the peptide binding cleft (8-10 aa)

alpha 3 interacts with CD8. it is structurally similar to beta-2 (via Ig constant region)and is relatively invariable.
what is the structure and function of the MHC II protein?
it's a heterodimer of alpha and beta chains, each is encoded for by different genes.

alpha 1/beta 1 = Ag binding cleft

alpha 2/beta 2 = CD4 contact area
is MHC Ag binding specific?
NO. a given MHC can bind a variety of Ag peptides
what is the difference between class I and II binding sites?
class I is BLOCKED at ends, holds smaller peptides and anchors the residues at #2 and #9.

class II is OPEN at ends, holds larger peptides (13-18) and anchors aren't specific. negatively charged position at #4, hydrophobic at #9.
what types of peptides do MHC class I molecules present?

where do the Ag and MHC associate?
endogenous peptides (ie viral)

Antigenic peptide and MHC I interact in the ER
how many MHC I molecules are present on the surface of a cell?
10^5
how many peptides are needed for recognition

what is their preferred chain length?
100 for recognition.

nonamers are preferred (8-10)
which amino acids are usually recognized by the TCR?
what is their structure?

which amino acids contact the MHC?
4-7 are usually recognized by the TCR. they form a 'bulge'.

1/2 and 8/9 contact the MHC.
where is the greatest degree of variability found within the MHC I?
alpha 1 & alpha 2 domains b/c they hold the antigenic peptide.
what types of peptides do MHC class II molecules present?

how are the peptides degraded?
they present exogenous peptides.

they are degraded via the endocytic pathway.
how large are the antigenic peptides bound by class II?
at least 13 amino acids. 9 amino acids are within the cleft.
what is the binding domain of class II? does the peptide bulge like in class I?
the binding domain is alpha 1/beta 1. there is a lesser bulge present.